Paracetamol: mostly harmless?… the sequel

Got a comment from my colleague – Dr Y Levy that got me thinking about fever, the big picture and all those little kids getting dosed up by well-meaning parents.  So I have revisited the Panadol debate

Here is what Hoods had to say in his comment:
“Way back in 1927 Julius Wagner-Jauregg won a nobel prize in medicine for showing the beneficial effects of fever in certain infectious diseases.
He delibrately infected his tertiary syphillis (general paresis of the insane) patients with malaria and they partially improved.
He then treated the malaria with quinine.
These days we treat all fevers with ceftriaxone”. [Ed: cynical, but sadly often true!]

Wagner-Jauregg won the Nobel Prize in 1927, joined the Nazi Party a few years later and did some reasonably (by todays standards) radical and semi-ethical experiments on the mentally ill of Austria back in the day.  Anyway, a fascinating citation – we have long ago been shown that fever can have some good effects on infectious disease and immune response.  But what recently?

I found a few interesting papers that support the fever defense hypothesis:

The Lancet, 1997 published this paper which was a small case-control study from Gabon, looking at paediatric malaria Plasmodium clearance – paracetamol vs. no paracetamol.  The outcome was 1) parasite clearance and 2) TNF / IL-6 / free radical production.   The kids getting paracetamol had the same amount of fever (trend towards less fever), but significantly longer parasite clearance times.  So it seemed paracetamol might have blunted the immune response – but it was a small trial and the mechanism is unclear.

 Prymula et al in Lancet 2009 ran a Czech study that looked at kids getting vaccinations – 2 groups: 1 with prophylactic paracetamol, 1 without.  What did they find?  Well the kids who got paracetamol were less likely to have a fever after vaccination, but they had significantly reduced antibody response to common vaccines – unclear if this correlates with in vivo reduction in immunity.

So to continue the soapbox lecture on paracetamol…..

The Big Picture – we work as doctors to treat symtoms, but also to achieve the best outcomes for our patients.  Fever is a symptom, not a disease.  Unfortunately most parents / patients do not make this distinction – from a patient  perspective a fever is a sign of illness, easily measured and remembered. The people that make and sell antipyretics have the easiest job in the world – paracetamol looks great to the patient – you take it and the fever abates – perfect!  Of course, we know it was going to swing down in an hour anyway, and then it returns a few hours later – just in time for the next dose!  This setup is marketing-gold!  Our patients and parents have been well trained by the TV, pharmacist and folklore to want to treat fever ASAP.

Fever is a harmless symptom in the vast majority of patients that we treat.  There is likely immune / host response benefit from fever.  Evolution tends to keep the bits that work, and fever looks like it has a beneficial function to the organism.  So I think I will agree with Dr Levy and other commenters…

Treating fever (in the absence of other symptoms) doesn’t really make sense –

  1. We might be interfering with a perfectly useful host defense mechanism
  2. Paracetamol works a bit, but you still get some fever and it will return in a few hours
  3. The reason you feel terrible when we get a virus etc is not just because of a fever – it is the result of a lot of factors, none of which antipyretics fix!
  4. The commonest Paeds toxicology OD scenario involves parents / health care professionals overdoing the dose / frequency of paracetamol.  So chasing fever with multiple doses of paracetamol might lead to serious mischief in some cases
Now, how do we go about changing one of the biggest behavioral automatisms of modern parents, nurses and medical staff?  Any suggestions?

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